factor X deficiency

Summary

factor X deficiency (MONDO:0002247) is a disease with 3 cohort genes and 4 clinical trials. Top therapeutic interventions include coagulation factor x human.

At a glance

• Cohort genes: 3
• ClinVar variants: 28
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	factor X deficiency
Mondo ID	MONDO:0002247
MeSH	D005171
NCIT	C131632
SNOMED CT	76642003
UMLS	C0015519
MedGen	4635
GARD	0023100
Is cancer (heuristic)	no

Data availability: 28 ClinVar variants.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › hematologic disorder › blood coagulation disease › coagulation protein disease › factor X deficiency

Related subtypes (27): factor XIII deficiency, factor VII deficiency, thrombophilia due to activated protein C resistance, hypoplasminogenemia, congenital high-molecular-weight kininogen deficiency, congenital factor XII deficiency, alpha-2-plasmin inhibitor deficiency, Tatsumi factor deficiency, East Texas bleeding disorder, inherited prekallikrein deficiency, congenital plasminogen activator inhibitor type 1 deficiency, thrombomodulin-related bleeding disorder, congenital vitamin K-dependent coagulation factors deficiency, hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation, multiple sclerosis-ichthyosis-factor VIII deficiency syndrome, congenital fibrinogen deficiency, combined deficiency of factor V and factor VIII, hemophilia, factor V deficiency, acquired coagulation factor deficiency, von Willebrand disease (hereditary or acquired), factor V short isoforms-related bleeding disorder, factor V amsterdam bleeding disorder, factor V atlanta bleeding disorder, combined deficiency of factor VII and factor X, plasminogen deficiency, type II, dysplasminogenemia

Subtypes (2): congenital factor X deficiency, acquired factor X deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

28 retrieved; paginated sample, class counts are floors:

13 pathogenic, 9 uncertain significance, 3 conflicting classifications of pathogenicity, 3 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1098484	NM_000504.4(F10):c.513del (p.Cys172fs)	F10	Pathogenic	criteria provided, single submitter
12053	NM_000504.4(F10):c.1096C>T (p.Arg366Cys)	F10	Pathogenic	no assertion criteria provided
12054	NM_000504.4(F10):c.814del (p.Ile271_Leu272insTer)	F10	Pathogenic	no assertion criteria provided
12056	NM_000504.4(F10):c.1012G>A (p.Val338Met)	F10	Pathogenic	no assertion criteria provided
12057	NM_000504.4(F10):c.1147C>T (p.Pro383Ser)	F10	Pathogenic	no assertion criteria provided
12058	NM_000504.4(F10):c.61G>A (p.Gly21Arg)	F10	Pathogenic	criteria provided, multiple submitters, no conflicts
12059	NM_000504.4(F10):c.859A>T (p.Arg287Trp)	F10	Pathogenic	no assertion criteria provided
12060	NM_000504.4(F10):c.1120T>C (p.Ser374Pro)	F10	Pathogenic	no assertion criteria provided
12062	NM_000504.4(F10):c.964G>A (p.Asp322Asn)	F10	Pathogenic	no assertion criteria provided
3573027	NM_000504.4(F10):c.307G>C (p.Asp103His)	F10	Pathogenic	no assertion criteria provided
12063	NM_000504.4(F10):c.140A>G (p.Glu47Gly)	F10-AS1	Pathogenic	no assertion criteria provided
12065	NM_000504.4(F10):c.214G>C (p.Glu72Gln)	F10-AS1	Pathogenic	no assertion criteria provided
1338738	NC_000013.11:g.109179481_114327244del	LOC130010104	Pathogenic	criteria provided, single submitter
1333006	Single allele	COL4A1	Likely pathogenic	criteria provided, single submitter
1679953	NM_000504.4(F10):c.1073C>T (p.Thr358Met)	F10	Likely pathogenic	criteria provided, single submitter
627253	NM_000504.4(F10):c.161A>G (p.Glu54Gly)	F10-AS1	Likely pathogenic	criteria provided, single submitter
12061	NM_000504.4(F10):c.424G>A (p.Glu142Lys)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
627251	NM_000504.4(F10):c.160G>A (p.Glu54Lys)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
988832	NM_000504.4(F10):c.1325G>A (p.Gly442Asp)	F10	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1098451	NM_000504.4(F10):c.28C>T (p.Leu10Phe)	F10	Uncertain significance	criteria provided, single submitter
1098452	NM_000504.4(F10):c.80G>A (p.Arg27His)	F10	Uncertain significance	criteria provided, single submitter
1098485	NM_000504.4(F10):c.829T>A (p.Cys277Ser)	F10	Uncertain significance	criteria provided, single submitter
1098486	NM_000504.4(F10):c.1387G>C (p.Asp463His)	F10	Uncertain significance	criteria provided, single submitter
619972	NM_000504.4(F10):c.872G>A (p.Arg291Gln)	F10	Uncertain significance	criteria provided, multiple submitters, no conflicts
1098480	NM_000504.4(F10):c.84G>T (p.Arg28Ser)	F10-AS1	Uncertain significance	criteria provided, single submitter
1098481	NM_000504.4(F10):c.89A>G (p.Gln30Arg)	F10-AS1	Uncertain significance	criteria provided, single submitter
1098482	NM_000504.4(F10):c.107C>A (p.Ala36Glu)	F10-AS1	Uncertain significance	criteria provided, single submitter
1098483	NM_000504.4(F10):c.152G>A (p.Gly51Glu)	F10-AS1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
COL4A1	Orphanet:36383	COL4A1/2-related familial vascular leukoencephalopathy
COL4A1	Orphanet:477749	Pontine autosomal dominant microangiopathy with leukoencephalopathy
COL4A1	Orphanet:481986	Familial schizencephaly
COL4A1	Orphanet:73229	HANAC syndrome
COL4A1	Orphanet:75326	Familial isolated retinal arteriolar tortuosity
COL4A1	Orphanet:899	Walker-Warburg syndrome
COL4A1	Orphanet:99810	Familial porencephaly
F10	Orphanet:328	Congenital factor X deficiency

Cohort genes → proteins

3 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
COL4A1	HGNC:2202	ENSG00000187498	P02462	Collagen alpha-1(IV) chain	clinvar
F10	HGNC:3528	ENSG00000126218	P00742	Coagulation factor X	clinvar
F10-AS1	HGNC:40225	ENSG00000231882		F10 antisense RNA 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
COL4A1	Collagen alpha-1(IV) chain	Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a ‘chicken-wire’ meshwork together with laminins, proteoglycans and entactin/nidogen.
F10	Coagulation factor X	Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	12.2×	0.159
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
COL4A1	Other/Unknown	no		Collagen_IV_NC, Collagen, CTDL_fold
F10	Protease	yes	3.4.21.6	EGF-type_Asp/Asn_hydroxyl_site, GLA_domain, EGF
F10-AS1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
placenta	1
right coronary artery	1
visceral pleura	1
liver	1
right lobe of liver	1
stromal cell of endometrium	1
hindlimb stylopod muscle	1
male germ line stem cell (sensu Vertebrata) in testis	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
COL4A1	283	ubiquitous	marker	visceral pleura, placenta, right coronary artery
F10	176	broad	marker	right lobe of liver, liver, stromal cell of endometrium
F10-AS1	122		yes	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, hindlimb stylopod muscle

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
COL4A1	2,909
F10	1,326
F10-AS1	0

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 1

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
F10	P00742	188
COL4A1	P02462	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 24. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective factor IX causes thrombophilia	1	1903.3×	0.004	F10
Defective cofactor function of FVIIIa variant	1	1903.3×	0.004	F10
Defective F9 variant does not activate FX	1	1903.3×	0.004	F10
Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus	1	634.4×	0.007	F10
Gamma-carboxylation of protein precursors	1	571.0×	0.007	F10
Removal of aminoterminal propeptides from gamma-carboxylated proteins	1	571.0×	0.007	F10
Anchoring fibril formation	1	380.7×	0.008	COL4A1
Amplification and propagation of coagulation cascade	1	317.2×	0.008	F10
Scavenging by Class A Receptors	1	300.5×	0.008	COL4A1
Fibronectin matrix formation	1	285.5×	0.008	COL4A1
Crosslinking of collagen fibrils	1	285.5×	0.008	COL4A1
Attachment of bacteria to epithelial cells	1	248.3×	0.008	COL4A1
Initiation of coagulation cascade	1	237.9×	0.008	F10
Laminin interactions	1	190.3×	0.009	COL4A1
Collagen chain trimerization	1	129.8×	0.011	COL4A1
Signaling by PDGF	1	126.9×	0.011	COL4A1
NCAM1 interactions	1	124.1×	0.011	COL4A1
Regulation of clotting cascade	1	116.5×	0.011	F10
Assembly of collagen fibrils and other multimeric structures	1	100.2×	0.013	COL4A1
Collagen degradation	1	87.8×	0.013	COL4A1
Collagen biosynthesis and modifying enzymes	1	85.2×	0.013	COL4A1
Non-integrin membrane-ECM interactions	1	77.2×	0.014	COL4A1
ECM proteoglycans	1	75.1×	0.014	COL4A1
Integrin cell surface interactions	1	67.2×	0.015	COL4A1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
renal tubule morphogenesis	1	2106.5×	0.006	COL4A1
retinal blood vessel morphogenesis	1	1203.7×	0.006	COL4A1
collagen-activated tyrosine kinase receptor signaling pathway	1	648.1×	0.008	COL4A1
blood vessel morphogenesis	1	401.2×	0.008	COL4A1
branching involved in blood vessel morphogenesis	1	263.3×	0.008	COL4A1
neuromuscular junction development	1	263.3×	0.008	COL4A1
basement membrane organization	1	255.3×	0.008	COL4A1
positive regulation of TOR signaling	1	247.8×	0.008	F10
cellular response to amino acid stimulus	1	153.2×	0.011	COL4A1
collagen fibril organization	1	112.3×	0.013	COL4A1
epithelial cell differentiation	1	87.8×	0.014	COL4A1
blood coagulation	1	86.9×	0.014	F10
brain development	1	39.8×	0.029	COL4A1
positive regulation of cell migration	1	30.9×	0.034	F10
proteolysis	1	17.1×	0.058	F10

Therapeutics

Drugs indicated for this disease

1 approved. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Coagulation Factor X Human	Approved (phase 4)

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 2

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
F10	ARGATROBAN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
F10	23	4
COL4A1	0	0
F10-AS1	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
ARGATROBAN	4	F10
FONDAPARINUX SODIUM	4	F10
FONDAPARINUX	4	F10
EDOXABAN	4	F10
RIVAROXABAN	4	F10
APIXABAN	4	F10
MELAGATRAN	4	F10
BETRIXABAN	4	F10
PENTAMIDINE	4	F10
DAREXABAN	3	F10
NAFAMOSTAT	3	F10
OTAMIXABAN	3	F10
DABIGATRAN	3	F10
GABEXATE	3	F10
LETAXABAN	2	F10
TANOGITRAN	2	F10
LY-517717	2	F10
RAZAXABAN	2	F10
GW813893	2	F10
EFEGATRAN	2	F10
SEGATROXABAN	2	F10
ERIBAXABAN	2	F10
FIDEXABAN	2	F10

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
F10	795	Binding:779, Functional:9, ADMET:7

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
F10	3.4.21.6	coagulation factor Xa

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
F10	795

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

23 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Compound	Max phase	Cohort target (bioactivity)
ARGATROBAN	4	F10
FONDAPARINUX SODIUM	4	F10
FONDAPARINUX	4	F10
EDOXABAN	4	F10
RIVAROXABAN	4	F10
APIXABAN	4	F10
MELAGATRAN	4	F10
BETRIXABAN	4	F10
PENTAMIDINE	4	F10
DAREXABAN	3	F10
NAFAMOSTAT	3	F10
OTAMIXABAN	3	F10
DABIGATRAN	3	F10
GABEXATE	3	F10
LETAXABAN	2	F10
TANOGITRAN	2	F10
LY-517717	2	F10
RAZAXABAN	2	F10
GW813893	2	F10
EFEGATRAN	2	F10
SEGATROXABAN	2	F10
ERIBAXABAN	2	F10
FIDEXABAN	2	F10

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	F10
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	COL4A1, F10-AS1

Undrugged target profiles

2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
COL4A1	0	—
F10-AS1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE3	3
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00930176	PHASE3	COMPLETED	A Study Investigating Treatment Factor X in People With Factor X Deficiency
NCT01086852	PHASE3	TERMINATED	Safety & Efficacy of BPL’s High Purity FACTOR X in Treatment of Factor X Deficient Subjects Undergoing Surgery
NCT01721681	PHASE3	COMPLETED	A Study to Investigate Bio Product Laboratory Ltd (BPL’s) Factor X in the Prophylaxis of Bleeding in Children <12 Years
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
COAGULATION FACTOR X HUMAN	4	3